New advances in circulating tumor cell­mediated metastasis of breast cancer (Review).

Breast cancer stands as the most prevalent form of cancer affecting women, with metastasis serving as a leading cause of mortality among patients with breast cancer. Gaining a comprehensive understanding of the metastatic mechanism in breast cancer is essential for early detection and precision treatment of the disease. Circulating tumor cells (CTCs) play a vital role in this context, representing cancer cells that detach from tumor tissues and enter the bloodstream of cancer patients. These cells travel in the blood circulation as single cells or clusters. Recent research has shed light on the enhanced metastatic potential of CTC clusters compared to single CTCs, despite their limited occurrence. The aim of the present review was to explore recent findings on CTCs with a particular focus on the clustering phenomenon of CTCs observed in breast cancer. Additionally, the present review delved into the comparison between single CTCs and CTC clusters regarding their implications for the treatment and prognosis of patients diagnosed with metastatic breast cancer. By examining the role and mechanisms of CTCs in breast cancer metastasis, the present review provided an improved understanding of CTCs and their significance in early detection of breast cancer metastasis through peripheral blood analysis. Moreover, it contributed to the comprehension of cancer prognosis and prediction by highlighting the implications of CTCs in these aspects. Ultimately, the present study seeks to advance knowledge in the field and pave the way for improved approaches to breast cancer management.

Interaction between tumor microenvironment, autophagy, and epithelial-mesenchymal transition in tumor progression.

Tumor microenvironment (TME) is the ecosystem surrounding a tumor to influence tumor cells' growth, metastasis and immunological battlefield, in which the tumor systems fight against the body system. TME has been considered as the essential link between the tumorigenesis and development of neoplasm. Both nutrients intake and tumor progression to malignancy require the participation of components in TME. Epithelial-mesenchymal transition (EMT) is a key step in the metastasis of tumor cells. Cells that lost polarity and acquired migration ability are prone to metastasize. Autophagy is an important self-protective mechanism in tumor cells and a necessity for the tumor cells to respond to harmful stress. Protective autophagy benefits tumor cells while abnormal autophagy leads to cell injury or death. EMT and autophagy are directly regulated by TME. To date, there are numerous studies on TME, autophagy and EMT separately, but few on their complex interrelationships. This review aims to comprehensively analyze the existing mechanisms and convincing evidence so far to seek novel therapeutic strategies and research directions.

The significance of time interval between perioperative SOX/XELOX chemotherapy and clinical decision model in gastric cancer.

Introduction: To investigate the influences of time interval between multimodality therapies on survival for locally advanced gastric cancer (LAGC) patients, 627 patients were included in a retrospective study, and 350 who received neoadjuvant chemotherapy (NACT) based on SOX (S-1 plus Oxaliplatin)/XELOX (Capecitabine plus Oxaliplatin) treatment, radical surgery, and adjuvant chemotherapy (AC) from 2005.01 to 2018.06 were eligible for analyses. Methods: Three factors were used to assess influences, including time interval from NACT accomplishment to AC initiation (PECTI), time to surgery after NACT accomplishment (TTS), and time to adjuvant chemotherapy after surgery (TAC). Results: Concerning PECTIs, 99 (28.29%) experienced it within 9 weeks, 188 (53.71%) within 9-13 weeks, 63 (18.00%) over 13 weeks. Patients' 5-year overall survival (OS) significantly decreased as trichotomous PECTI increased (78.6% vs 66.7% vs 55.7%, P = .02). Analogously, there was a significant decrease for dichotomous TTS (within vs over 5 weeks) in OS (P = .03) and progression free survival (PFS) (P = .01) but not for dichotomous TAC (within vs over 6 weeks) in OS and PFS (P = .40). Through multivariate Cox analyses, patients with PECTI over 13 weeks had significantly worse OS (P = .03) and PFS (P = .02). Furthermore, extended TTS had significantly worse OS and PFS but insignificantly worse OS and PFS than extended TAC. Therefore, gastric patients receiving perioperative SOX/XELOX chemotherapy and surgery with extended PECTI over 9 weeks or TTS over 5 weeks would have a negative correlation with PFS and OS, and worse when PECTI over 13 weeks. Nomograms (including PECTI, ypT, ypN, Area Under Curve (AUC) = 0.81) could predict patient survival probability and guide intervention with net benefit. Discussion: In control of PECTI, TTS could be extended appropriately, and shortened TAC might make a remedy, and delayed TAC might be allowed when TTS was shortened.

Neoadjuvant chemoradiotherapy followed by laparoscopic distal gastrectomy in advanced gastric cancer: A case report and review of literature.

BACKGROUND: The laparoscopic technique has been widely applied for early gastric cancer, with the advantages of minimal invasion and quick recovery. However, there is no report about the safety and oncological outcome of laparoscopic gastrectomy with D2 lymph node dissection for patients after neoadjuvant chemoradiotherapy. CASE SUMMARY: A 60-year-old man was diagnosed with advanced distal gastric cancer, cT4aN1M0 stage III. The neoadjuvant chemoradiotherapy was performed based on the regimen of gross tumor volume 50G y/25 f and clinical target volume 45 Gy/25 f, as well as concurrent S-1 60 mg Bid. Then laparoscopic distal gastrectomy with D2 lymph node dissection was undertaken successfully for him after achieving partial response evaluated by radiological examination. The patient recovered smoothly without moderate or severe postoperative complications. The postoperative pathological stage was ypT3N0M0 with American Joint Committee on Cancer tumor regression grade 1. He was still in good condition after 5 years of follow-up. CONCLUSION: Neoadjuvant chemoradiotherapy followed by laparoscopic technique could be applicable and may achieve satisfactory oncological outcomes. Our finding requires further validation by cohort studies.

Comparison of tumor regression grading systems for locally advanced gastric adenocarcinoma after neoadjuvant chemotherapy.

BACKGROUND: Current tumor regression grade (TRG) evaluations are based on various systems which brings confusion for oncologists and pathologists when interpreting results. The recent six-tier system (JGCA2017-TRG) recommended by the Japanese Gastric Cancer Association (JGCA) is worth investigating, as four-tier TRG systems are favored in various parts of the world. AIM: To compare the predictive accuracies of five published TRG systems. METHODS: Data were retrospectively collected from patients with locally advanced gastric cancer (LAGC) who underwent neoadjuvant chemotherapy followed by D2 Lymphadenectomy between January 2005 and January 2014 at our institution. Outcomes were overall survival (OS) and disease-free survival (DFS), which were evaluated separately using the following TRG systems: JGCA2017, JGCA, Becker, AJCC/CAP, and Mandard. RESULTS: All five published TRG systems were independent predictors for OS and DFS. Concordance indices of the JGCA2017, JGCA, Becker, AJCC/CAP-TRG, and Mandard systems were 0.651/0.648 0.652/0.649, 0.693/0.695, 0.688/0.685, and 0.674/0.675 for OS and DFS, respectively. The four-tier Becker system showed the highest c-index, which was significantly greater than that of the six-tier JGCA2017 and five-tier JGCA systems (P < 0.05 in OS and DFS). When residual tumor percentages were reset as: "no residual tumor", < 10%, < 100%, and "no response", the rearranged cutoff values achieved a maximum c-index with 0.728 for OS and 0.737 for DFS, which was superior to the other five systems. CONCLUSION: The newly introduced six-tier JGCA-TRG system cannot increase prognostic stratification. The four-tier Becker system is more suitable for LAGC patients. A population-based study is warranted to define the optimal criterion for TRG in LAGC patients.

Membranous Nephropathy in Pregnancy.

BACKGROUND: Primary membranous nephropathy (pMN) is less common in women of child-bearing age. The kidney risk factors to adverse maternal-fetal outcomes and the effects of pregnancy on pMN process need to be investigated. METHODS: We retrospectively screened all the patients with biopsy-proven pMN from 2008 to 2018. Any cases of pregnancy that occurred at the time of pMN diagnosis or during follow-up were included in the study. Clinical and pathological data were collected from all patients at the time of kidney biopsy and their gestational results were recorded. RESULTS: Of the 27 pregnancies with gestational time of 35.9 ± 4.5 weeks, 10 adverse maternal-fetal events occurred, including fetal loss (11%), preterm delivery (26%), and severe preeclampsia (15%). The kidney parameters were relatively stable with all preserved kidney function. Time-averaged urinary protein (p < 0.001) and serum albumin (p < 0.001), maximum urinary protein (p = 0.001) and minimum serum albumin (p = 0.01) before week 20, anti-phospholipase A2 receptor (PLA2R) positivity (p = 0.03), and no remission during pregnancy (p = 0.004) were risk factors to adverse maternal-fetal outcomes. Time-averaged urinary protein and serum albumin correlated with the birth weight percentile of neonates. CONCLUSIONS: Pregnancy in pMN patients showed risks to adverse maternal-fetal events. Heavy proteinuria, especially before week 20 of gestation, severe hypoalbuminemia, positive anti-PLA2R, and no remission were risk factors to worse outcomes.

Intermolecular Amination of Unactivated C(sp3 )-H Bonds with Cyclic Alkylamines: Formation of C(sp3 )-N Bonds through Copper/Oxygen-Mediated C(sp3 )-H/N-H Activation.

The first example of intermolecular amination of unactivated C(sp3 )-H bonds by cyclic alkylamines mediated by Cu(OAc)2 /O2 is reported. This method avoids the use of benzoyloxyamines as the aminating reagent, which are normally prepared from alkylamines in extra steps. A variety of unnatural ß2, 2 -amino acid analogues are synthesized by this simple and efficient procedure. This approach offers a solution to the previous unmet challenge of C(sp3 )-H/N-H activation for the formation of C(sp3 )-N bonds.

Pd(II) -Catalyzed Intermolecular Amination of Unactivated C(sp(3) )-H Bonds.

Pd(II) -catalyzed intermolecular amination of unactivated C(sp(3) )-H bonds has been successfully developed for the first time. This method provides a new way to achieve the challenging intermolecular amination of unactivated C(sp(3) )-H bonds, producing a variety of unnatural ß(2) -amino carboxylic acid analogues. This C(sp(3) )-H amination protocol is demonstrated with a broad substrate scope, good functional-group tolerance, and chemoselectivity. It is operated without use of phosphine ligand or external oxidant.

Histone chaperone-mediated nucleosome assembly process.

A huge amount of information is stored in genomic DNA and this stored information resides inside the nucleus with the aid of chromosomal condensation factors. It has been reported that the repeat nucleosome core particle (NCP) consists of 147-bp of DNA and two copies of H2A, H2B, H3 and H4. Regulation of chromosomal structure is important to many processes inside the cell. In vivo, a group of histone chaperones facilitate and regulate nucleosome assembly. How NCPs are constructed with the aid of histone chaperones remains unclear. In this study, the histone chaperone-mediated nucleosome assembly process was investigated using single-molecule tethered particle motion (TPM) experiments. It was found that Asf1 is able to exert more influence than Nap1 and poly glutamate acid (PGA) on the nucleosome formation process, which highlights Asf1's specific role in tetrasome formation. Thermodynamic parameters supported a model whereby energetically favored nucleosomal complexes compete with non-nucleosomal complexes. In addition, our kinetic findings propose the model that histone chaperones mediate nucleosome assembly along a path that leads to enthalpy-favored products with free histones as reaction substrates.